ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundSeveral experimental and clinical studies suggest that cyclosporin A (CSA) treatment reduces transplant atherosclerosis. Because oxidized LDL (oxLDL) is believed to play a key role in the development of atherogenesis, causing injury to the endothelium, and has been shown to induce apoptosis of endothelial cells, we investigated whether CSA inhibits oxLDL-induced apoptosis.Methods and Results-Apoptosis was induced in human umbilical venous endothelial cells (HUVECs) by incubation of 10 [micro sign]g/mL oxLDL for 18 hours. Coincubation with CSA dose dependently decreased oxLDL-induced apoptosis, with a maximal effect at 10 [micro sign]mol/L. In addition, tumor necrosis factor-alpha- and angiotensin II-induced apoptosis was significantly prevented by CSA treatment, suggesting a general apoptosis-suppressive effect of CSA. CSA has been shown to inhibit disruption of the mitochondrial membrane function, which plays a key role in apoptosis induction. Indeed, oxLDL treatment triggered the release of cytochrome C from the mitochondria into the cytosol, indicating disturbance of the mitochondrial membrane. CSA (10 [micro sign]mol/L) completely inhibited the oxLDL-induced release of cytochrome C. Moreover, tumor necrosis factor-alpha- and angiotensin II-induced cytochrome C release was prevented by CSA treatment.ConclusionsOxLDL induces dysfunction of the mitochondrial membrane, leading to cytochrome C release into the cytosol, and thereby stimulates apoptosis of human endothelial cells. Apoptosis suppression by CSA correlates with the prevention of mitochondrial dysfunction and thus indicates the importance of mitochondrial destabilization in oxLDL-induced apoptosis signaling. The inhibition of apoptosis by CSA might preserve the function of the endothelium and may at least in part contribute to the antiatherogenic effects of CSA in transplant atherosclerosis. (Circulation. 1998;98:1153-1157.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundEpidemiological studies indicate that estrogen replacement therapy decreases the risk of cardiovascular events in postmenopausal women. Estrogen may confer cardiovascular protection by improving endothelial function because it increases endothelium-dependent vasodilation. It is not known whether progesterone attenuates the beneficial effects of estrogen on endothelial function.Methods and Results-Seventeen postmenopausal women with mild hypercholesterolemia were enrolled in a placebo-controlled, crossover trial to evaluate the effect of transdermal estradiol, with and without vaginal micronized progesterone, on endothelium-dependent vasodilation in a peripheral conduit artery. Brachial artery diameter was measured with high-resolution B-mode ultrasonography. To assess endothelium-dependent vasodilation, brachial artery diameter was determined at baseline and after a flow stimulus induced by reactive hyperemia. To assess endothelium-independent vasodilation, brachial artery diameter was measured after administration of sublingual nitroglycerin. During estradiol therapy, reactive hyperemia caused an 11.1 +/- 1.0% change in brachial artery diameter compared with 4.7 +/- 0.6% during placebo therapy (P<0.001). Progesterone did not significantly attenuate this improvement. During combined estrogen and progesterone therapy, flow-mediated vasodilation of the brachial artery was 9.6 +/- 0.8% (P=NS versus estradiol alone). Endothelium-independent vasodilation was not altered by estradiol therapy, either with or without progesterone, compared with placebo. There was a modest decrease in total and LDL cholesterol during treatment both with estradiol alone and when estradiol was combined with progesterone (all P<0.001 versus placebo). In a multivariate analysis that included serum estradiol, progesterone, total and LDL cholesterol concentrations, blood pressure, and heart rate, only the estradiol level was a significant predictor of endothelium-dependent vasodilation.ConclusionsThe addition of micronized progesterone does not attenuate the favorable effect of estradiol on endothelium-dependent vasodilation. The vasoprotective effect of hormone replacement therapy may extend beyond its beneficial actions on lipids. (Circulation. 1998;98:1158-1163.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundPlatelet/endothelium interaction plays an important role in the pathophysiology of inflammation and atherosclerosis. The role of platelets for monocyte chemotactic protein-1 (MCP-1) secretion and surface expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells has been assessed.Methods and Results-Monolayers of human umbilical vein endothelial cells were incubated with nonstimulated or ADP-activated platelets for 6 hours, and secretion of MCP-1 and surface expression of ICAM-1 were determined by ELISA and flow cytometry, respectively. In the presence of ADP-activated platelets, both MCP-1 secretion and ICAM-1 surface expression were significantly increased compared with nonstimulated platelets (P<0.02). Activation of the transcription factor nuclear factor-kappa B (NF-kappa B) determined by electrophoretic mobility shift assay and kappa B-dependent transcriptional activity was enhanced in the presence of activated platelets. In addition, ADP-activated platelets induced MCP-1 and ICAM-1 promoter-dependent transcription. Liposomal transfection of a double-stranded kappa B phosphorothioate oligonucleotide, but not of the mutated form, inhibited MCP-1 secretion and surface expression of ICAM-1 on activated endothelium (P<0.05).ConclusionsThe present study indicates that activated platelets modulate chemotactic (MCP-1) and adhesive (ICAM-1) properties of endothelial cells via an NF-kappa B-dependent mechanism. Platelet-induced activation of the NF-kappa B system might contribute to early inflammatory events in atherogenesis. (Circulation. 1998;98:1164-1171.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundLipoprotein(a) is a risk factor for coronary artery disease. Although it has been implicated in restenosis after balloon angioplasty, its role in restenosis within coronary stents is unknown. The aim of the study was to assess the role of plasma lipoprotein(a) as a predictor for restenosis after elective coronary stenting.Methods and Results-Elective, high-pressure stenting of de novo lesions in native coronary arteries with Palmaz-Schatz stents was performed in 325 consecutive patients. Clinical, angiographic, and biochemical data were analyzed prospectively. Angiographic follow-up was performed at 6 months. Lipoprotein(a) levels were compared in patients with and without restenosis. Angiographic follow-up was obtained in 312 patients (96%); recurrence was observed in 67 patients (21.5%). No clinical or biochemical variable was associated with restenosis. Lipoprotein(a) level was 37.81 +/- 49.01 mg/dL (median, 22 mg/dL; range, 3 to 262 mg/dL) in restenotic patients and 36.95 +/- 40.65 mg/dL (median, 22 mg/dL; range, 0 to 244 mg/dL) in nonrestenotic patients (P=NS). The correlations between percent diameter stenosis, minimum luminal diameter, and late loss at follow-up angiography and basal lipoprotein(a) plasma level after logarithmic transformation were 0.006, 0.002, and 0.0017, respectively. Multiple stents were associated with a higher incidence of restenosis (P=0.006), but biochemical data in these patients were similar to those treated with single stents.ConclusionsThe basal plasma level of lipoprotein(a) measured before the procedure is not a predictor for restenosis after elective high-pressure coronary stenting. (Circulation. 1998;98:1172-1177.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundLeft ventricular assist devices (LVADs) are frequently used as a bridge to cardiac transplantation and may be useful as long-term therapy. The purpose of this study was to compare the exercise performance of LVAD patients with that of ambulatory heart failure patients.Methods and Results-Exercise testing with hemodynamic and respiratory gas measurements was performed in 65 congestive heart failure (CHF) patients (age 53 +/- 10 years) and 20 LVAD patients (age 49 +/- 8 years). Peak VO2was significantly higher in the LVAD than the CHF patients (CHF, 12 +/- 3; LVAD, 15.9 +/- 3.8 mL [middle dot] kg-1[middle dot] min-1; P<0.001), as was the VO2at the anaerobic threshold (CHF, 8.1 +/- 2.1; LVAD, 12.2 +/- 2.9 mL [middle dot] kg-1[middle dot] min-1; P<0.001). At rest, mean arterial blood pressure (CHF, 87 +/- 11; LVAD, 94 +/- 9 mm Hg) and cardiac output (CHF, 4 +/- 1; LVAD, 4.9 +/- 0.9 L/min) were increased, whereas mean pulmonary artery pressure (CHF, 28 +/- 11; LVAD, 18 +/- 4 mm Hg) and pulmonary artery wedge pressure (CHF, 16 +/- 10; LVAD 5 +/- 3 mm Hg) were reduced (all P<0.01). At peak exercise, heart rate (CHF, 125 +/- 24; LVAD, 148 +/- 24 bpm), blood pressure (CHF, 87 +/- 14; LVAD, 96 +/- 12 mm Hg), and cardiac output (CHF, 7.6 +/- 2.2; LVAD, 11.2 +/- 2.6 L/min) were higher (all P<0.01), whereas mean pulmonary artery pressure (CHF, 48 +/- 12; LVAD, 30 +/- 5 mm Hg) and mean pulmonary capillary wedge pressure (CHF, 31 +/- 11; LVAD, 14 +/- 6 mm Hg) were lower in the LVAD group (both P<0.001). In the LVAD patients, Fick cardiac output was higher than LVAD flow sensor value measurements (Fick, 11.6 +/- 2.5; LVAD, 8.1 +/- 1.2 L/min; P<0.001).ConclusionsHemodynamic measurements at rest and during exercise are significantly improved in patients with devices compared with those in ambulatory heart failure patients awaiting cardiac transplantation. Similarly, the exercise capacity of device patients is better than that of transplant candidates and in the majority of patients is similar to that of patients with mild CHF. (Circulation. 1998;98:1178-1183.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Backgroundbeta-Blockers have improved symptoms and reduced the risk of cardiovascular events in studies of patients with heart failure, but it is unclear which end points are most sensitive to the therapeutic effects of these drugs.Methods and Results-We combined the results of all 18 published double-blind, placebo-controlled, parallel-group trials of beta-blockers in heart failure. From this combined database of 3023 patients, we evaluated the strength of evidence supporting an effect of treatment of left ventricular ejection fraction, NYHA functional class, hospitalizations for heart failure, and death. beta-Blockers exerted their most persuasive effects on ejection fraction and on the combined risk of death and hospitalization for heart failure. beta-Blockade increased the ejection fraction by 29% (P<10-990% of the trials were eliminated from the analysis or if a large number of trials with a neutral result were added to the analysis. In contrast, the effect of beta-blockade on NYHA functional class was of borderline significance (P=0.04) and disappeared with the addition or removal of only 1 moderate-size study. Although beta-blockade reduced all-cause mortality by 32% (P=0.003), this effect was only moderately robust and varied according to the type of beta-blocker tested, ie, the reduction of mortality risk was greater for nonselective beta-blockers than for beta1-selectiveagents (49% versus 18%, P=0.049). However, selective and nonselective beta-blockers did not differ in their effects on other measures of clinical efficacy.ConclusionsThese analyses indicate that there is persuasive evidence supporting a favorable effect of beta-blockade on ejection fraction and the combined risk of death and hospitalization for heart failure. In contrast, the effect of these drugs on other end points requires additional study. (Circulation. 1998;98:1184-1191.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundEndothelial dysfunction of coronary arteries with impaired vasodilation has been reported in patients with arterial hypertension. However, the effect of dynamic exercise on coronary vasomotion of a stenotic vessel segment before and after PTCA has not yet been evaluated in these patients.Methods and Results-Coronary vasomotion of a normal and a stenotic vessel segment was studied in 39 patients with coronary artery disease during supine bicycle exercise before and 9 +/- 3 months after PTCA. Luminal area changes were determined by biplane quantitative coronary arteriography. There were 21 normotensive and 18 hypertensive patients who did not differ with regard to clinical characteristics. Percent area stenosis decreased after PTCA from 90% to 39% (P<0.001) in normotensive and from 86% to 33% (P<0.001) in hypertensive patients. Exercise-induced vasomotion of the normal vessel segment was significantly different between normotensives and hypertensives before (+19% versus +1%, P<0.01) and after (+16% versus +3%, P<0.01) PTCA. In contrast, stenotic vessel segments showed vasoconstriction in both normotensive and hypertensive patients (Delta exercise, -11% versus -20%, P=NS), which was reversed after PTCA (+3% versus +2%, P=NS).ConclusionsNormal coronary arteries show reduced vasodilation during exercise in hypertensive patients that may be explained by the presence of endothelial dysfunction. Stenotic vessels demonstrate paradoxical vasoconstriction during exercise in both normotensive and hypertensive patients. PTCA reverses vasoconstriction by elimination of the flow-limiting stenosis and prevention of coronary stenosis narrowing during exercise in normotensive and hypertensive patients. (Circulation. 1998;98:1192-1197.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundAnimal experiments and epidemiological studies have suggested that high potassium intake may reduce the risk of stroke, but the evidence is inconclusive, and the role of other nutrients in potassium-rich foods remains unknown.Methods and Results-We examined the association of potassium and related nutrients with risk of stroke among 43 738 US men, 40 to 75 years old, without diagnosed cardiovascular diseases or diabetes, who completed a semiquantitative food frequency questionnaire in 1986. During 8 years of follow-up, 328 strokes (210 ischemic, 70 hemorrhagic, 48 unspecified) were documented. The multivariate relative risk of stroke of any type for men in the top fifth of potassium intake (median intake, 4.3 g/d) versus those in the bottom (median, 2.4 g/d) was 0.62 (95% CI, 0.43, 0.88; P for trend=0.007). Results for ischemic stroke alone were similar. Intakes of cereal fiber and magnesium, but not of calcium, were also inversely associated with risk of total stroke. These inverse associations were all stronger in hypertensive than normotensive men and were not materially altered by adjustment for blood pressure levels. Use of potassium supplements was also inversely related to risk of stroke, particularly among men taking diuretics (relative risk, 0.36; 95% CI, 0.18, 0.72).ConclusionsAlthough these data do not prove a causal relationship, they are consistent with the hypothesis that diets rich in potassium, magnesium, and cereal fiber reduce the risk of stroke, particularly among hypertensive men. Potassium supplements may also be beneficial, but because of potential risks, use should be carefully monitored and restricted to men taking potassium-losing diuretics. (Circulation. 1998;98:1198-1204.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundThe effective orifice area (EOA) of a prosthetic valve is superior to transvalvular gradients as a measure of valve function, but measurement of mitral prosthesis EOA has not been reliable.Methods and Results-In vitro flow across St Jude valves was calculated by hemispheric proximal isovelocity surface area (PISA) and segment-of-spheroid (SOS) methods. For steady and pulsatile conditions, PISA and SOS flows correlated with true flow, but SOS and not PISA underestimated flow. These principles were then used intraoperatively to calculate cardiac output and EOA of newly implanted St Jude mitral valves in 36 patients. Cardiac output by PISA agreed closely with thermodilution (r=0.91, Delta =-0.05 +/- 0.55 L/min), but SOS underestimated it (r=0.82, Delta =-1.33 +/- 0.73 L/min). Doppler EOAs correlated with Gorlin Equation estimates(r=0.75 for PISA and r=0.68 for SOS, P<0.001) but were smaller than corresponding in vitro EOA estimates.ConclusionsProximal flow convergence methods can calculate forward flow and estimate EOA of St Jude mitral valves, which may improve noninvasive assessment of prosthetic mitral valve obstruction. (Circulation. 1998;98:1205-1211.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID